chr2-96327298-T-C

Variant names:

• chr2-96327298-T-C
• rs753719371
• NM_001008949.3:c.667T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001008949.3(ITPRIPL1):​c.667T>C​(p.Phe223Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITPRIPL1 NM_001008949.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.91
• Publications: 0 publications found

Genes affected

ITPRIPL1 (HGNC:29371): (ITPRIP like 1) Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008949.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIPL1	NM_001008949.3	MANE Select	c.667T>C	p.Phe223Leu	missense	Exon 3 of 3	NP_001008949.1	Q6GPH6-1
	ITPRIPL1	NM_178495.6		c.691T>C	p.Phe231Leu	missense	Exon 1 of 1	NP_848590.3
	ITPRIPL1	NM_001163523.2		c.643T>C	p.Phe215Leu	missense	Exon 2 of 2	NP_001156995.1	Q6GPH6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIPL1	ENST00000439118.3	TSL:1 MANE Select	c.667T>C	p.Phe223Leu	missense	Exon 3 of 3	ENSP00000389308.2	Q6GPH6-1
	ITPRIPL1	ENST00000420728.1	TSL:2	c.760T>C	p.Phe254Leu	missense	Exon 2 of 2	ENSP00000396552.1	H7C0T2
	ITPRIPL1	ENST00000361124.5	TSL:6	c.691T>C	p.Phe231Leu	missense	Exon 1 of 1	ENSP00000355121.4	Q6GPH6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251356 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0068	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.66		Loss of ubiquitination at K225 (P = 0.069)
MVP		0.54
MPC		0.68
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.41
gMVP		0.50
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs753719371; hg19: chr2-96993036;